title: Recombinant human prion protein inhibits prion propagation in vitro.
abstract: Prion diseases are associated with the conformational conversion of the cellular prion protein (PrP(C)) into the pathological scrapie isoform (PrP(Sc)) in the brain. Both the in vivo and in vitro conversion of PrP(C) into PrP(Sc) is significantly inhibited by differences in amino acid sequence between the two molecules. Using protein misfolding cyclic amplification (PMCA), we now report that the recombinant full-length human PrP (rHuPrP23-231) (that is unglycosylated and lacks the glycophosphatidylinositol anchor) is a strong inhibitor of human prion propagation. Furthermore, rHuPrP23-231 also inhibits mouse prion propagation in a scrapie-infected mouse cell line. Notably, it binds to PrP(Sc), but not PrP(C), suggesting that the inhibitory effect of recombinant PrP results from blocking the interaction of brain PrP(C) with PrP(Sc). Our findings suggest a new avenue for treating prion diseases, in which a patient's own unglycosylated and anchorless PrP is used to inhibit PrP(Sc) propagation without inducing immune response side effects.
authors.affiliation: 1] Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA [2] National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA [3].
authors.forename: Jue
authors.initials: J
authors.lastname: Yuan
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Zhan
authors.forename: Romany
authors.initials: R
authors.lastname: Abskharon
authors.forename: Xiangzhu
authors.initials: X
authors.lastname: Xiao
authors.forename: Manuel Camacho
authors.initials: MC
authors.lastname: Martinez
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Zhou
authors.forename: Geoff
authors.initials: G
authors.lastname: Kneale
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Mikol
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
authors.forename: Witold K
authors.initials: WK
authors.lastname: Surewicz
authors.forename: Joaquín
authors.initials: J
authors.lastname: Castilla
authors.forename: Jan
authors.initials: J
authors.lastname: Steyaert
authors.forename: Shulin
authors.initials: S
authors.lastname: Zhang
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.forename: Alexandre
authors.initials: A
authors.lastname: Wohlkonig
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Zou
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism / Q000473:pathology*; D013045:Species Specificity
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011994:Recombinant Proteins